This study will investigate the relation between postmenopausal endogenous levels of estrogens and subsequent development of endometrial cancer. In premenopausal women, estrogens unopposed by progesterone are known to stimulate endometrial cell division, providing a rationale for the role of estrogens in endometrial carcinogenesis. In postmenopausal women, estrogen replacement therapy is associated with an increased risk of endometrial cancer. However, there is no direct epidemiologic evidence that the physiologically low levels of endogenous estrogens observed after menopause are positively associated with endometrial cancer risk. In the face of increasing long-term use of estrogen replacement therapy, to prevent cardiovascular disease and osteoporosis, a better understanding of the role of endogenous estrogens may help develop prescription guidelines. The proposed study will use an existing resource of frozen serum samples collected between 1985 and 1991 in a cohort of 6071 postmenopausal women enrolled in a study of breast cancer and endogenous hormones (New York University Women's Health Study, NYUWHS). The specific aims of the proposal are: 1) to identify incident cases of endometrial cancer, using follow-up information generated by the NYUWHS until mid-1998; 2) to conduct a case-control study of endometrial cancer nested within this cohort. Sixty incident cases of endometrial cancer are expected to occur by the end of follow-up. For each case, four controls, matched on age and date of blood donation, will be selected. Controls will have to be alive, free of disease and with an intact uterus at time of diagnosis of the case. Information on known risk factors will be collected through telephone interviews. Serum samples will be assayed for estrone, estradiol, percent estradiol bound to sex hormone binding globulin and percent free estradiol. Conditional logistic regression for matched data will be used to assess whether higher levels of endogenous estrogens are associated with a higher risk of endometrial cancer. The study will also investigate whether the role of obesity in endometrial cancer can be explained by its action on endogenous estrogens.